Aim: MIH is a special entity with a characteristic clinical appearance of developmentally defective enamel of the FPM and often also of the permanent incisors. Such developmental enamel defects may also be present on other teeth, including the SDM.
The aim of the study was to determine whether any of the studied environmental and/or genetic factors or genetic variants affect the development of MIH. The literature describes a number of different environmental factors that are present during the formation of FPM and permanent incisors, which supposedly influence the development of MIH. In addition, there is also a probability of certain genetic factors influencing the development of MIH. Despite numerous research the etiology of MIH remains unclear.
Furthermore, I was interested in whether the mineralisation of the enamel of SDM is worse in patients with MIH compared to subjects without MIH, and whether there is a higher prevalence of caries among subjects with MIH compared to subjects without MIH.
Hypotheses: (1) MIH develops under the influence of certain environmental factors. (2) The development of MIH is also influenced by a genetic predisposition or the presence of genetic variants in the enamelin gene (ENAM). (3) Mineralisation of the SDM crown is worse in patients with MIH compared to subjects without MIH. (4) A higher prevalence of caries is expected in subjects with MIH compared to subjects without MIH.
Methods and subjects: The teeth of all 113 subjects (born in 2004, who underwent surgical treatment in early childhood at the Clinic of Otorhinolaryngology and Cervicofacial Surgery, University Medical Center Ljubljana) were examined according to an established protocol under standardized conditions. In accordance with the recommendations, a MIH clinical data recording sheet and caries detection criteria were used. Data on potential environmental factors that could affect the development of MIH were obtained through questionnaires and from the medical records of subjects at the Clinic for Otorhinolaryngology and Cervicofacial Surgery, University Medical Center Ljubljana. In the DNA, isolated from a sample of the subject's peripheral blood, I determined the presence of HLA DQ2 and HLA DQ8 haplotypes and SNP in the ENAM gene (rs3796704), in the TTLL12 gene (rs13058467) and in the genes that interact with the ENAM gene (AMBN: rs546778141, AMTN: rs7660807, AMTN: rs35286445, COL14A1: rs4870723, MMP20: rs2245803 and TUFT1: rs3828054). Genotypes were determined using TaqMan genotyping assays, high-resolution melting analysis, and Sanger sequencing.
Subjects were divided into two groups; the first group contained subjects showing signs of MIH, and the second group subjects without any signs of MIH. Univariate logistic regression or the odds ratio test was used to determine statistically significant differences between the groups. The difference in the number of caries affected tooth surfaces between the groups was tested using the Mann-Whitney U test, while the potential correlation between the presence of investigated polymorphisms and MIH was tested using the Cochran-Armitage test and the Fisher exact test. P-values of 0.05 or less were considered statistically significant. Data were statistically analyzed using SPSS 24.0 (IBM Corp., Armonk, NY, USA) and GraphPad Prism version 8 (GraphPad Software, San Diego, CA, USA).
Results: Among the studied environmental factors, I did not confirm a statistically significant correlation with the development of MIH. However, the study of genetic predispositions suggests a statistically significant correlation between the presence of SNP rs2245803 in its homozygous form in the MMP20 gene and the development of MIH. The presence of genetic variants in the ENAM gene did not have a significant effect on the development of MIH. Differences in the mineralisation of the SDM crowns in subjects with MIH and those without MIH could not be confirmed due to an insufficient number of physiologically exfoliated teeth. However, I confirmed a higher prevalence of caries in subjects with MIH compared to subjects without MIH.
Conclusion: To date, the environmental and/or genetic factors that influence the development of MIH remain unknown. MIH most likely develops as a result of a simultaneous or synergistic effect of several environmental and genetic factors.